Project Summary A significant and detrimental component of alcohol use disorder (AUD) is the disruption in decision-making processes. Individuals with AUD show persistent deficits in decision-making processes leading to a shift to habitual control over actions as a consequence of an impaired goal-directed system. Chronic ethanol experience is believed to produce alterations in the neural circuits of reward and decision-making and likely contributes to the difficulty in maintaining abstinence for individuals with AUD. However, very little is known of the specific neural mechanisms through which ethanol dependence disrupts goal-directed decision-making. Recently, we identified long-lasting ethanol dependence-induced projection and cell-type specific disruptions to goal- directed decision-making circuits that result in habitual control. We found that ethanol dependence disrupted the goal-directed circuit in which orbital frontal cortex (OFC) neurons showed a long-lasting decrease in intrinsic excitability. Strikingly, orbitostriatal projection neurons also showed reduced transmission onto the direct, but not indirect, output pathway of the dorsomedial striatum (DMS). Furthermore, increasing the activity of OFC projection neurons was sufficient to restore goal-directed control in ethanol dependent mice. Based on our recent work on CIE-induced alterations of a goal-directed circuit, we formed the central hypothesis of this proposal: Alcohol dependence results in a bias towards habitual control over actions by disrupting goal- directed circuits. We have evidence to show that ethanol dependence disrupts goal-directed decision-making by attenuating neurotransmission of a known goal-directed circuit. However, attenuated OFC-DMS transmission was measured in an ex vivo slice preparation, which begs the question, how does CIE exposure alter OFC-DMS transmission in vivo, in awake behaving animals? Experiments in Aim 1 will focus on understanding how CIE alters OFC-DMS plasticity in vivo and whether a change in connectivity contributes to disrupted decision- making processes. In addition, we have shown that a change in OFC transmission can have a major influence on decision-making processes but it is unknown how attenuated OFC-DMS transmission alters DMS output. To address this, Aim 2 will investigate whether changes in OFC function are sufficient to alter striatal output to modulate goal-directed actions. Elucidating the effects of ethanol dependence in vivo, specifically on OFC-DMS transmission and DMS output, will further our understanding of the CIE-induced disruption of goal-directed actions and the resulting habitual control.